Antisense oligonucleotides: towards clinical trials.

Antisense oligonucleotides have the ability to selectively block disease-causing genes, thereby inhibiting production of disease-associated proteins. The specificity and application of antisense oligonucleotides have been strongly validated in animal models for various disease targets. Based on the pharmacological, pharmacodynamic and pharmacokinetic profiles, the first generation of antisense oligonucleotides--phosphorothioates--have reached the stage of human clinical trials for various diseases. While ongoing human clinical trials are being carried out to further establishing the safety and efficacy of these oligonucleotides, the experience gained is providing a basis for designing a second generation of antisense oligonucleotides.